Interesting - XMRV & Autism

[mojoey]

So Mikovitz is trying to disparage another lab ... has she actually read their paper? If you read the Cooperative paper, you will see that their sample volume was larger than WPI's in the original Science study. This test was run with fresh full blood draws, full tubes, and was designed to help validate the WPI finding. Even their earlier finger-prick test used a larger sample volume than some of the other XMRV tests. That is a well proven method for retrovirus detection, now used in HIV testing.

Anyway, the Cooperative study is just one view, their finding might be right or wrong, but building a scientific consensus must be a non-political, evidence-based process. For Mikovitz to make comments like that discredits her and WPI.

Does sample size matter if you use the wrong methodology? If Coop were so confident about their testing, why did they yank their commercial XMRV test from the market?

 

[kurt]

Does sample size matter if you use the wrong methodology? If Coop were so confident about their testing, why did they yank their commercial XMRV test from the market?

No, sample size does not matter if the methods are invalid. But the point was about sample volume. The method disagreement is more serious, and too specific to retrovirology for me to comment on. There are very competent people on both sides of this disagreement, the issue is not credentials, or methodology, or sample size, it is whether or not XMRV is a valid finding. And finding a new retrovirus is a very complex issue with a history of many false positives and many false negatives even across multiple studies.

I can't say exactly why Coop removed their test, but don't believe they lost confidence in their test.

One point that might not have been made yet that probably should be mentioned. This Cooperative study was run before WPI came out with their clarification on how to find XMRV, I believe they published that last Spring? This study was based on the original Science article only.

 

[Esther12]

If they came to believe that the WPI's claims were wrong, and there was no link between CFS and XMRV then pulling their test from the market for CFS patients was the only responsible thing to do. Maybe it was wrong of them to market a test without having first tested it upon positive patients though - I'm not sure what the norm is. It seems like everyone expect XMRV to be easier to find that it has turned out to be.

 

[Cort]

If they came to believe that the WPI's claims were wrong, and there was no link between CFS and XMRV then pulling their test from the market for CFS patients was the only responsible thing to do. Maybe it was wrong of them to market a test without having first tested it upon positive patients though - I'm not sure what the norm is. It seems like everyone expect XMRV to be easier to find that it has turned out to be.

That could be. CD took quite a bit of blood from a group of patients, gathered data on them and tested them for free in an effort to figure out what was going on.

I think they felt based on their ability to find XMRV in prostate tissues that finding it in CFS patients would be a snap - particularly since the Science paper was so strong. I think they were as surprised as anyone that it didn't work out. They thought this was a hot market for them - there's no reason in the world for a diagnostic lab not to want to find the next big thing is diagnostic testing.

Ditto with retrovirologists - they may be right or they may be wrong and some are now taking positions on XMR (which is another matter) but why wouldn't a retrovirologist just love to find another human retrovirous?

These are methodological disputes nothing more in my opinion.

 

[Cort]

I swear to fulfill, to the best of my ability and judgment, this covenant:
I will respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow.
I will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism.
I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon's knife or the chemist's drug.
I will not be ashamed to say "I know not," nor will I fail to call in my colleagues when the skills of another are needed for a patient's recovery.

If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.

This is the Thruth in the eyes of the beholder, the doctors who sweare this oath. I know it' s a fine motto and doesn't apply to hypocritical oafs

Love,
Berthe

http://www.onwilliglichaam.blogspot.com

Is that the Hippocratic Oath? If so - its a good one!

 

[mojoey]

If they came to believe that the WPI's claims were wrong, and there was no link between CFS and XMRV then pulling their test from the market for CFS patients was the only responsible thing to do. Maybe it was wrong of them to market a test without having first tested it upon positive patients though - I'm not sure what the norm is. It seems like everyone expect XMRV to be easier to find that it has turned out to be.

I don't agree with this logic. If a patient wants to test for a virus, and Coop believes they have the best commercial test to test for that virus, how is it irresponsible of Coop to offer a commercial test for said virus? Especially when they know VIPdx is continuing to offer a commercial test, wouldn't it be responsible to offer what they believe to be a better test to the public instead of "letting" VIPdx corner the market and give out what Coop believes to be false results?

In other words, if you're speaking from both a financially competitive and morally responsible standpoint, the ends (giving patients what they want--the best test) should justify the means (finding all negatives).

 

[natasa778]

I

know Cooperative and they fully expected to be confirming WPI's results, based on the Science paper. Their finding surprised them as much as everyone else, particularly given the higher sensitivity of their testing.

their paper was submitted in May 2010! instead of questioning their blood handling and methodology after other zero studies had been heavily criticised and detailed methodology published in Science... after it became obvious that all zero findings were most probably seriously flawed... instead of taking a back seat and re-examining why they'd come up with absolutely NOTHING in any human sample, they go on to publish!?

and not only publish but say THAT THEY ARE DOING THAT OUT OF CONCERN FOR THE PATIENT!!!!!???!!!!!! now where have we heard that gem before I wonder

Good intentions? for God's sake give me a break.

Unf*%*believable!

 

[asleep]

These labs are running their best tests and simply do not find any XMRV. That is the entire story, no conspiracy, no hidden agenda, no anti-CFS mindset, and no fraud. They are definitely not incompetent, they are just scientists and this is often the way science works.

I've addressed this elsewhere, but this attitude of a priori dismissal of ignoble motives is wildly naive, esp given the past actions of certain people and agencies with respect to this disease. Ditto with the idea that science is some holy pursuit utterly devoid of politics and human failure of any form. Just look at the example of the guy who discovered h pylori and had to infect himself before others would listen. And I tend to think that the potential of the WPI's discovery is far more politically and socially consequential than finding the cause of stomach ulcers (not to denigrate the suffering they cause).

Given the massive tide of money, power, vested interests, careers, ignorance, etc that the WPI is swimming against, to hold them to the same standard as their would-be deniers is shameful.

I know Cooperative and they fully expected to be confirming WPI's results, based on the Science paper. Their finding surprised them as much as everyone else, particularly given the higher sensitivity of their testing.

Did I stumble into some sort of viral PR campaign here? What's with the obsequious, fawning respect for a lab that couldn't find XMRV and then concludes that their inability to find it means it doesn't exist? For the umpteenth time, absence of evidence is not evidence of absence, esp if XMRV requires a paradigm shift in our understanding of viral detection (as appears possible, if not likely). Cooperative Diagnostic's blatant disregard for this simple truth should elicit a stark suspicion of their competence and/or motives.

I think they felt based on their ability to find XMRV in prostate tissues that finding it in CFS patients would be a snap - particularly since the Science paper was so strong. I think they were as surprised as anyone that it didn't work out. They thought this was a hot market for them - there's no reason in the world for a diagnostic lab not to want to find the next big thing is diagnostic testing.

Ditto with retrovirologists - they may be right or they may be wrong and some are now taking positions on XMR (which is another matter) but why wouldn't a retrovirologist just love to find another human retrovirous?

These are methodological disputes nothing more in my opinion.

Again with the fawning and equivocating and apologetics. Please stop ascribing rosy motives and desires to people whose public actions and words are indistinguishable from an attempt to bury the XMRV finding. Given the political and social context in which this is playing out, the WPI deserves the benefit of the doubt. At least until someone scientifically proves why the WPI and Lo/Alter conclusions are wrong rather than simply undermining them with unproven hypotheses and whisper campaigns.

You are correct in your last sentence, though: these are fundamentally methodological disputes. Yet virtually none of these 0/0 studies even acknowledge this as a possibility. Why would a competent, well-meaning scientist do that?

 

[Cort]

I

their paper was submitted in May 2010! instead of questioning their blood handling and methodology after other zero studies had been heavily criticised and detailed methodology published in Science... after it became obvious that all zero findings were most probably seriously flawed... instead of taking a back seat and re-examining why they'd come up with absolutely NOTHING in any human sample, they go on to publish!?

and not only publish but say THAT THEY ARE DOING THAT OUT OF CONCERN FOR THE PATIENT!!!!!???!!!!!! now where have we heard that gem before I wonder

Good intentions? for God's sake give me a break.

Unf*%*believable!

Here's the thing - you may believe that there's something wrong with their methodology and I may believe that but Cooperative Diagnostics does not. Why would you put your name on a paper you believe or know is fatally flawed?? You wouldn't do that - you would never publish a paper you thought wouldn't hold up - particularly in a closely watched field like this. The only viable answer to your question that I can see is that they firmly believe they are right and given that they probably do believe they are doing the patients a favor.

We have groups all over the place with diametrically opposed beliefs each of which believes they are doing patients a favor. That's why we have all this controversy! At least with XMRV researchers should be able to come to a consensus who's right.

 

[dannybex]

Cooperative Diagnostic's blatant disregard for this simple truth should elicit a stark suspicion of their competence and/or motives.
...

Please stop ascribing rosy motives and desires to people whose public actions and words are indistinguishable from an attempt to bury the XMRV finding.

???

Why in the world would a private lab that could make millions from it's test want to 'bury the XMRV finding'?

 

[muffin]

A stretch on this one but...

April 29th, 2010
SC Launch invests in Cooperative Diagnostics (Press Release by SCRA)
SCRAs SC Launch Invests $200,000 in Cooperative Diagnostics, Presents Knowledge Economist Awards at Coffee and Conversation Event http://www.codiagnostics.com/about/Apr29_10.pdf

SCRA gave Coop $200K. If you look at SCRA's website you will see that they are involved in the Government (Mclean, VA office) in many areas including defense and health. Now, it is only $200K, but SCRA is probably making a lot more money from the Feds and might have put pressure on Coop to knock it off with any XMRV/Retrovirus study.

Yes, even Paranoids have enemies - stretch but with the government doing its best to damage and kill off real research, I just would not put anything past the Feds (or small groups within the government, really).

 

[mojoey]

Here's the thing - you may believe that there's something wrong with their methodology and I may believe that but Cooperative Diagnostics does not. Why would you put your name on a paper you believe or know is fatally flawed?? You wouldn't do that - you would never publish a paper you thought wouldn't hold up - particularly in a closely watched field like this. The only viable answer to your question that I can see is that they firmly believe they are right and given that they probably do believe they are doing the patients a favor.

We have groups all over the place with diametrically opposed beliefs each of which believes they are doing patients a favor. That's why we have all this controversy! At least with XMRV researchers should be able to come to a consensus who's right.

Hey Cort,

Maybe you can answer my question since Kurt hasn't responded. If they believe they have the best test, why do you think they stopped offering it on the open market? Wouldn't they be doing patients more of a favor by diluting the market share of a competitor (which is using a faulty test), and hence decreasing the number of false positives?

I admit, if they continued to offer their commercial test, I might buy for a second that they actually believe they're confident in their results. When you do only clinical research testing and have the backing of the CDC (which also coincidentally could not find a single positive XMRV sample), it becomes an easy moral "out" because even if your test isn't the best, the responsibility of validating it is now shared with a highly respected governmental agency. A faulty test is much harder to justify when you're primarily offering it commercially, because you're under the scrutiny of both customers demanding the right answers, regulating agencies, competitor labs, researchers etc, and all you really have is your brand and the true quality of your test to deflect criticism.

I don't mind hearing defense of Cooperative Diagnostics, because I'd truly like to believe their test is a continually evolving product of competitive spirits, but the logic behind these arguments seems to be more 'let's give them benefit of the doubt", and less rational skepticism.

 

[asleep]

???

Why in the world would a private lab that could make millions from it's test want to 'bury the XMRV finding'?

I'm not going to speculate, nor am I even accusing them of trying to bury the finding.

I am simply making the point that the conclusion they draw in their study is vastly overreaching and logically flawed. A competent, well-meaning researcher would not draw this conclusion w/o at least acknowledging that their result might merely indicate methodological insufficiencies on their part (esp when there is much talk of that possibility). It also just so happens that the conclusion that CD draws in their study is, from the outside, exactly the kind of conclusion one would draw if trying to help bury the finding.

So if one refrains from speculating on motives (unlike those who wish to faithfully paint CD and these other 0/0 studies as well-meaning), what are we left with? We have a study that draws a disproportionate conclusion that looks, from an objective outside perspective, indistinguishable from the types of games Wessely and Reeves et al have been playing for decades. You can freely jump on the "well, they couldn't possibly be ill-intentioned" bandwagon, but to me their actions and words, independent of motive speculation, raise serious red flags.

 

[anciendaze]

I'm going to try to clarify my own position, at the risk of igniting more useless argument.

I do not ascribe to conspiracy theories in general, except as all organizations with insiders are conspiracies. What I see over and over are human beings acting like human beings, and ignoring their own limitations, or those of organizations and institutions. Circular reasoning is spotted quickly if the circle is small. Make it large enough, and throw in enough confusing detail, and it passes inspection from those who should know better.

Medical research is much easier if you can avoid the messy world of sick patients. Once a respectable group gets away with this, a kind of Gresham's law sets in. Precedent makes it easier for others to take this short cut without accepting responsibility for a logical fallacy. (In any case, the fallacy is now distributed over multiple groups.) This has taken place with the question of positive control samples. We have some groups moving away from reliance on samples from patients.

They can push the sensitivity of tests to extraordinary lengths, but if the test is based on an assumption about how the virus ought to behave, when the virus is doing something different, it tells you nothing about clinical disease. The idea that people in a hurry will take shortcuts should not surprise anyone who drives an automobile. That sometimes the shortcuts are mistakes should not surprise any insurance adjuster.

If this were easy it would have been done many years ago. The low-hanging fruit of infectious disease has already been picked. It should be almost axiomatic that the remaining challenges will be harder, and the diseases which have defied explanation will violate common assumptions in the field.

 

[Esther12]

I don't agree with this logic. If a patient wants to test for a virus, and Coop believes they have the best commercial test to test for that virus, how is it irresponsible of Coop to offer a commercial test for said virus? Especially when they know VIPdx is continuing to offer a commercial test, wouldn't it be responsible to offer what they believe to be a better test to the public instead of "letting" VIPdx corner the market and give out what Coop believes to be false results?

In other words, if you're speaking from both a financially competitive and morally responsible standpoint, the ends (giving patients what they want--the best test) should justify the means (finding all negatives).

But they believe that they have important information which their customers do not have - that XMRV is not related to CFS.

Given this disparity they would feel guilty making money from what they see as the ignorance of their customers. I wouldn't want to make money out of people by selling them a product which I think is useless to them. It wouldn't be illegal, but it's not something I'd feel morally comfortable with.

People like Reeves and Wessely clearly have their own interests in this, but I don't think all the negative studies should be seen as disingenuous. It does seem like XMRV is more difficult to detect than was expected (or is not related to CFS) and that alone could serve to explain coop's actions.

 

[asleep]

I'm going to try to clarify my own position, at the risk of igniting more useless argument.

I do not ascribe to conspiracy theories in general, except as all organizations with insiders are conspiracies. What I see over and over are human beings acting like human beings, and ignoring their own limitations, or those of organizations and institutions. Circular reasoning is spotted quickly if the circle is small. Make it large enough, and throw in enough confusing detail, and it passes inspection from those who should know better.

Medical research is much easier if you can avoid the messy world of sick patients. Once a respectable group gets away with this, a kind of Gresham's law sets in. Precedent makes it easier for others to take this short cut without accepting responsibility for a logical fallacy. (In any case, the fallacy is now distributed over multiple groups.) This has taken place with the question of positive control samples. We have some groups moving away from reliance on samples from patients.

They can push the sensitivity of tests to extraordinary lengths, but if the test is based on an assumption about how the virus ought to behave, when the virus is doing something different, it tells you nothing about clinical disease. The idea that people in a hurry will take shortcuts should not surprise anyone who drives an automobile. That sometimes the shortcuts are mistakes should not surprise any insurance adjuster.

If this were easy it would have been done many years ago. The low-hanging fruit of infectious disease has already been picked. It should be almost axiomatic that the remaining challenges will be harder, and the diseases which have defied explanation will violate common assumptions in the field.

Bingo! Couldn't have said it better myself.

To relate this to the point I'm trying to make: In light of the current atmosphere, studies that double down on the current assumptions rather than acknowledge a possible need for a paradigm shift should be, at best, taken with a grain of salt.

 

[urbantravels]

I co-sign anciendaze's post as well.

I don't think the negative studies were all undertaken wholly in bad faith. I think most of them were quick and dirty attempts to find the virus using techniques most researchers assumed were adequate. These studies didn't replicate the methods of Lombardi just because everyone was out to discredit the WPI - the researchers simply proceeded from the assumption that it wasn't necessary to replicate the exact methods of Lombardi. One needn't assume bias or malicious intent - just a failure of imagination.

Now, if you posit that one particular group or another *did* have a bias or an agenda, that might make them extra-not-zealous to go to great lengths to replicate Lombardi's methods, but that wouldn't change the outcome unless they were deliberately falsifying results in some way. And if you're falsifying, why give your study a 0/0 result? As someone said, zero is rarely the right answer in science.

I think the memo has been pretty widely distributed by now that there is an issue with detection and assays that remains to be resolved, and scientists who read the negative studies will read them with that in mind. I'm somewhat impatient to see things get to a point where peer reviewers will bust negative studies for poor methodology, instead of letting zero/zero studies sail through while (presumably) new positive studies will be given the special fine tooth comb treatment before they're allowed to be published. The current situation makes for a frustrating limbo, because we KNOW so much is in the pipeline that's going to blow the field wide open, but it just can't quite happen yet before things get published. However, the end result will be a batch of negative studies that were weak and will ultimately be disregarded, and positive studies that will be unusually strong.

 

[George]

I'm with Anciendaze.

The Lipkin Study is being designed in such a way as prove a link one way or another. It's not down to what Lipkin finds but instead it will show clear winners and losers in the ability to find the virus and it's design will clearly rule out contamination. Such an air tight study is what we "need". The NIH seems pretty hopeful/assured that this study will put ME/CFS on the map. They also seem pretty assured that the study will lay to rest any charges coming from people who haven't been able to find it. That's what we want right???

 

[mojoey]

But they believe that they have important information which their customers do not have - that XMRV is not related to CFS.

Given this disparity they would feel guilty making money from what they see as the ignorance of their customers. I wouldn't want to make money out of people by selling them a product which I think is useless to them. It wouldn't be illegal, but it's not something I'd feel morally comfortable with.

People like Reeves and Wessely clearly have their own interests in this, but I don't think all the negative studies should be seen as disingenuous. It does seem like XMRV is more difficult to detect than was expected (or is not related to CFS) and that alone could serve to explain coop's actions.

I still don't buy it. Negative results have nothing to do with the usefulness of a test -- the usefulness is in the accuracy of the result. A clinical trial for a drug that doesn't work is a very useful clinical trial. A commercial test for contaminants in drinking water that finds no such contaminants is very useful if there are actually no contaminants. So on and so forth.

I can't think of a single other example where distribution of a product has been stopped out of guilt for providing value in truth.

 

[Esther12]

I still don't buy it. Negative results have nothing to do with the usefulness of a test -- the usefulness is in the accuracy of the result. A clinical trial for a drug that doesn't work is a very useful clinical trial. A commercial test for contaminants in drinking water that finds no such contaminants is very useful if there are actually no contaminants. So on and so forth.

I can't think of a single example where distribution of a product has been stopped out of guilt for providing value in truth.

The logic behind this argument is so faulty it's absurd.

Would it be morally sound to sell a test for Spiritual Misallignment if no-one is spiritually misalligned, and the test accurately turns up 100% negative results to all customers for $700 a pop.

If coop are using the PCR methods the Science paper said should be able to detect XMRV in patients blood, but they're finding no positives at all and believe the WPI's results are due to contamination, then I don't think it's at all surprising that they'd pull the test. That's not to say that they're right, but those beliefs would explain their actions.